Simian Virus 40 (SV40) transformation provides an in vitro model for cell changes accompaning viral oncogenesis. The frequency of this event varies with the cell line studied. Past studies have indicated that certain human cell lines (including those from patients with Down's Syndrome and Fanconi's anemia) have an increased susceptibility to transformation by SV40. Clinical data show that these patients also have an increased incidence of various types of cancer. I plan to reexamine these observations in the cell lines already studied as well as in others (including Xeroderma pigmentosum, Bloom's, Gardner's, Peutz-Jeghers' and the Basal cell nevus syndromes as well as other stable trisomies and translocations). The criteria for identification of transformation will include: altered colonial morphology, presence of SV40 viral T antigen, ability to grow in soft agar, and fibrinolysis. If the observation can be confirmed that the differences in transformation susceptibility are eliminated by infection with isolated viral DNA, I propose study of adsorption of viral particles by the cell lines. The adsorption assay will measure the efficiency of binding of infectious particles to the cells rather than radioactively labeled particles which may not be all biologically active. The intracellular fate of SV40 will be studied both by measuring the deoxyribonuclease susceptibility of labeled viral DNA and by using viral mutants with structural proteins either altered (e.g., tsD mutant) or absent (e.g., deletion mutants) which are known to have effects on uncoating and/or infection. Finally, hybridization of "low" and "high" susceptibility cell lines can show whether susceptibility to SV40 viral transformation involves factors which have dominant function in a heterokaryon. In addition, chromosome study of such cells may help to identify the location of critical cellular genes affecting the process.